Tetanus is an acute disease caused by a neurotoxin produced by the anaerobe Clostridium tetani with motor and autonomous nervous system manifestations such as rigidity and convulsive spasms. Neonatal tetanus (NT) is around 10% in these countries where antenatal care is also well below 50%. According to the latest WHO estimates in 2010, NT claimed 58,000 newborn lives and is still a major public health concern. Mothers and newborns are at high risk when delivery and umbilical cord stump are performed under unsanitary conditions leading to tissue infection. The Centers of Disease Control and Prevention (CDC) and World Health Organization (WHO) recommend vaccinations of pregnant women at 20 weeks of gestation against tetanus and other preventable diseases due to increased rate of complications in mothers and their fetuses. These immunizations not only confer protective immunity to the mother, but also provide a passive immune response to the infant prior to the development of their own antibodies. Maternal antibodies are transferred through the umbilical cord blood during fetal development and breast milk during infant nursing. Thus, two doses of tetanus toxoid can reduce mortality from neonatal tetanus by 94%.
Although tetanus is a vaccine preventable disease, it has not been fully eradicated despite the efforts of Maternal and Neonatal Tetanus (MNT) Elimination Initiative launched by UNICEF, WHO and UNFPA in 1999. The problem of inadequate vaccine coverage is more critical in developing countries where many women do not receive vaccinations before pregnancy due to limited access to health care providers. For the same reason, pregnant women deliver their babies in non-sanitary conditions resulting in high mortality rates from tetanus infections. A critical bottleneck for effective vaccination is the absence of electricity in rural areas of developing countries, which is required for vaccine transportation and storage at low temperatures.
Tetanus toxoid is a small protein with low immunogenicity, so the vaccine has low potency and requires the presence of an adjuvant (Alum) and multiple immunization doses to induce robust antibody titers and affinity maturation.
To this day tetanus infections claim at least 60,000 maternal and neonatal lives worldwide. Two doses of adjuvanted tetanus vaccine are recommended to protect pregnant women during labor and their newborns, but in many areas vaccination is still unavailable or insufficient.
It has been demonstrated that pregnancy hormones modulate maternal immunity to tolerate the developing fetus, but a downside of tolerance is the increased rate and severity of infections due to compromised immune responses. Pregnant women infected with influenza virus are at higher risk than healthy non-pregnant controls. Influenza infection-induced inflammation may compromise the well-being of their offspring by stillbirth, preterm labor, small for gestation age newborns, fetal abnormalities and even death. The Centers of Disease Control and Prevention (CDC) and World Health Organization (WHO) recommend vaccinations of pregnant women at 20 weeks of gestation against preventable diseases including tetanus, due to higher risk of complications in mothers and their fetuses. These immunizations not only confer protective immunity to the mother, but also provide a passive immune response to the infant prior to the development of their own antibodies. Maternal antibodies are transferred through the umbilical cord blood during fetal development and breast milk during infant nursing.
The problem of inadequate vaccine coverage is more critical in developing countries where many women do not receive these vaccines before pregnancy and frequently they do not have access to health care providers delivering their babies in non-sanitary conditions resulting in high mortality rates from tetanus infections. Moreover, intramuscular delivery of tetanus toxoid requires the presence of an adjuvant (Alum) due to low vaccine potency, and multiple immunization doses to induce robust antibody titers and affinity maturation.
Vaccine delivery in the skin has been shown to utilize antigen presenting cells (APCs) residing in the epidermis and the dermis, which leads to an increased immune response compared to the traditional route of intramuscular delivery. Skin vaccination during pregnancy via intradermal injection can be more immunogenic than intramuscular vaccine delivery.
What is needed are methods, compositions and devices for tetanus immunization.
There is a continuing need for methods, compositions and devices for tetanus immunization.